The present invention relates to micromanipulators, and more particularly to Huxley-style micromanipulators and devices useful therein.
A common challenge in studying the physical properties of single cells is the stable and reproducible positioning of transducers. This situation occurs, for example, in force measurements on single cardiac cells or in voltage-clamp studies on dialyzed cells which require that electronics be combined with the suction micropipette holder. The experimental challenge is compounded when precise measurement of contractile shortening and electrical behavior are combined since convenient alignment of the optical sensor used in the former measurement requires that it be mounted separately from the mechanically isolated microscope system. In this example, it is advantageous to have a means for remote control of micromanipulation, and ideally this should not utilize conductive leads, which can introduce potential sources of electrical noise near the experimental preparation
The micromanipulator designed by A.F Huxley has the ability to bear large weights in a stable fashion. It is an assembly of metals bars stapped together with pieces of spring metal that also serve as a weight-bearing fulcrum In principle, displacement of the micrometer drive by 2-5 .mu.m is reduced at least fivefold by lever action, thus permitting precise and reproducible repositioning at the submicron level The manipulator's elegant and simple design enables the construction of suitable, relatively inexpensive models by researchers.
Nonetheless, the Huxley-style micromanipulator has not proven to be entirely satisfactory in practice. Its "footprint" is too large for particular applications due to the three large micrometers located in its base. Tilt of the axes of micromanipulation is achieved by tipping of the whole manipulator with an unavoidable resultant effect on the axial alignment of the fine control. Additionally, only three axes of control (that is, three degrees of freedom) are available. The layout of the micrometers dictates the provision of separate right- and left-handed models for right- and left-handed operators.
Remote control of the Huxley-style manipulator can be achieved by replacement of each of its three micrometer drives by stepping motors. This approach adds a major expense to the basic price of the micromanipulator, and it introduces electrical leads near the experimental system. Alternatively, a remote control using a hydraulic drive has been offered commercially, but this requires factory installation, adds significant space to the "footprint" of the unit, and cannot be retrofitted easily to many existing manipulators. Moreover, the hydraulic drive totally replaces the micrometer drive so that the original micrometer control is sacrificed to the remote controller.
Narishige U.S. Pat. Nos. 4,526,169; 4,679,976 and 4,700,584 disclose hydraulic control of a micromanipulator. The Narishige actuator is based on a rubberized deformable rolling diaphragm. The micrometer head is used as a means for transmitting a variation in hydraulic or hydrostatic pressure, with the variations in hydraulic pressure being transduced into displacements of a piston. As the hydraulic actuator is based on the confinement of a non-compressible fluid entrained between deformable membranes which roll and unroll, the relationship between micrometer input and output microtool position can be affected by hydrostatic pressure because the initial outward bulging of the membranes at the neutral position is oppositely related to the respective changes in the shape of the membranes as one piston advances and the other recedes.
In the most recent of the Narishige micromanipulators, the hydraulic cylinder is constituted by a cylinder body formed interiorly with a hydraulic chamber and rolling diaphragm. Displacement of a micrometer piston causes a variation of the force with which the piston presses the diaphragm. This causes a pressurizing or depressurizing of the hydraulic chamber within the cylinder body. The variation in pressure of the hydraulic chamber within the cylinder body is transmitted via a tube to the hydraulic cylinder of the pressure reception section of the moving arm, to thereby vary the pressure of the hydraulic chamber within the cylinder body of the moving section. For example, if the interior of the hydraulic cylinder is pressurized, the pressure in the hydraulic cylinder will increase, thereby causing the diaphragm to press the piston and move the lever arm.
Like the Huxley-style micromanipulators the Narishige micromanipulators have their limitations and have not proven to be entirely acceptable in use. While visual repositioning with a Narishige micromanipulator is good, "blind" repositioning is not as reproducible and investigators commonly experience significant drift. Because of the use of the rolling, flexible diaphragm, the dependency of the Narishige micromanipulator on the use of hydraulic pressure necessarily introduces potential sources of error. Changes in the pressure exerted on the output end of the micromanipulator (e.g., the microtool) are reflected in the hydraulic pressure within the micromanipulator and thus the positioning of the output end. For example, any change in the weight of the microtool held by the output end of the micromanipulator or any change in its effective weight (for example, as a result of an acceleration or deceleration of the microtool) will be reflected in the hydraulic pressure. While Narishige teaches the need for minimizing thermal effects on the hydraulic fluid through the use of a thermal fluid having a relatively low thermal coefficient of expansion and other means, no fully effective thermal compensation is provided Finally, any hydraulic coupling together of the Narishige actuators governing separate axes of control results in undesirable interaction between the actuators because the changes in pressure on the deformable membranes can cause the volume of a hydraulic chamber to be altered despite the fact that the piston in the driver actuator is held fixed by a micrometer.
Accordingly, it is an object of the present invention to provide a Huxley-type micromanipulator having remote control which is either added to the micrometer control without adding to the footprint of the micromanipulator or used as a substitute therefor so as to enable a smaller footprint for the micromanipulator.
Another object is to provide such a micromanipulator which can afford tilting of particular axes without tilting of the micromanipulator base, can provide more than three axes of control, and which do not require separate right- and left-handed versions.
A further object is to provide a micromanipulator utilizing hydraulic controls which are substantially insensitive within limits to the load place on the micromanipulator output, and which permit coupling, scaling, tilt, and additional degrees of freedom to be provided without interaction between hydraulic systems.
It is another object of the present invention to provide a device enabling automatic compensation for the thermal expansion of the fluid in the hydraulic control of a micromanipulator or like device.
It is also an object to provide a more compact Huxley-style micromanipulator.